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TNF-induced enterocyte apoptosis and detachment in mice: induction of caspases and prevention by a caspase inhibitor, ZVAD-fmk |
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Published in | Laboratory investigation. 1999, vol. 79, no. 4, p. 495-500 | |
Abstract | Injection of mouse recombinant TNF to mice induced apoptosis and detachment of the enterocytes of the tip of the villi, evident after 30 to 90 minutes, which resulted in a shrinkage of the villi. Injection of TNF increased the expression of caspase 1, 2, 3, and 6 as well as of cathepsin D in the mucosal wall, which was maximal 30 minutes after TNF injection. Caspase 1 and 3 were not induced in TNFR1-deficient mice in which TNF does not induce apoptosis and detachment. The administration of a caspase inhibitor (ZVAD-fmk, 300 microg) decreased enterocyte detachment and apoptosis, as well as villus atrophy, whereas a caspase 3 inhibitor (Z-DEVD-cmk) had no effect. The results indicate that the induction of caspases by TNF is the cause of their detachment in the lumen and of the resulting villus atrophy. | |
Keywords | Amino Acid Chloromethyl Ketones/pharmacology — Animals — Antigens, CD/genetics/metabolism/physiology — Apoptosis/drug effects/physiology — Cell Adhesion/drug effects/physiology — Cysteine Proteinase Inhibitors/pharmacology — DNA Fragmentation — Intestinal Mucosa/cytology/drug effects/pathology — Mice — Mice, Inbred C57BL — Mice, Inbred CBA — Mice, Knockout — Receptors, Tumor Necrosis Factor/genetics/metabolism/physiology — Receptors, Tumor Necrosis Factor, Type I — Recombinant Proteins/pharmacology — Tumor Necrosis Factor-alpha/pharmacology | |
Identifiers | PMID: 10212002 | |
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Research group | Facteurs influençants le développement pulmonaire: étude translationnelle chez l'animal et l'homme (182) | |
Citation (ISO format) | PIGUET, Pierre et al. TNF-induced enterocyte apoptosis and detachment in mice: induction of caspases and prevention by a caspase inhibitor, ZVAD-fmk. In: Laboratory investigation, 1999, vol. 79, n° 4, p. 495-500. https://archive-ouverte.unige.ch/unige:74361 |